Reactive oxygen species treatment in the management of wounds

Bacterial and fungal biofilms are a significant problem in many clinical settings particularly wounds and soft tissue lesions by virtue of their increased tolerance towards conventionally prescribed antimicrobials (Percival and Bowler, 2004; Davis et al, 2006; Dryden et al, 2017a). Antibiotic use in such conditions (chronic wounds, burns, certain surgical sites, prosthetic devices, chronic respiratory conditions and cystic fibrosis, recurrent cystitis) leads to intense selective pressure often resulting in further antibacterial resistance. Alternative therapeutic strategies that can improve antimicrobial efficacy towards biofilms, thereby limiting antibiotic use and reducing the development of further resistance would be of considerable benefit (Dryden et al, 2017b). One such development may be the use of topical therapy with Reactive Oxygen Species (ROS) in heavily colonised lesions with a host inflammatory response which is often referred to as ‘slough’ . This will be referred to as ‘critical colonisation’ . (Dryden et al, 2017a). Therapies involving ROS as a mechanism of action are already available in clinical use for wounds and are being developed for clinical use in other settings (Dunnil et al, 2015; Dryden et al, 2017a; Dryden et al, 2017b). There is a global antibiotic resistance crisis which may limit therapeutic choices in the future (WHO, 2014; Davies 2013). Governments and professional groups are developing antimicrobial resistance (AMR) strategies that include programs of antimicrobial stewardship (Department of Health and Department for Environment, Food and Rural Affairs, 2013; AMR Review, 2016). Such a program has recently been published specifically for wound care (Lipsky et al, 2016). The more widespread use of ROS in wounds to reduce bacterial bioburden may prevent extension of critical colonisation to deeper infection and reduce the requirements for systemic antimicrobials. The first entirely novel antimicrobial agent to reach early clinical use is one employing reactive oxygen species (ROS) as its mechanism of action and this is specifically for wound treatment (Dryden et al, 2016). Currently available wound ROS therapy is in the form of a honey delivery mechanism — SurgihoneyROTM— not to be confused with other pharmaceutical grade honeys. SurgihoneyRO is engineered honey which delivers therapeutic levels of ROS at constant, steady concentrations over a prolonged period. A synthetic ROS gel is in production. Bacterial colonisation and biofilm production with subsequent inflammation and infection is a huge global health problem in wounds especially in diabetes, burn victims, the elderly. In an era of increasing antimicrobial resistance, there are few entirely novel antimicrobial agents in development and antibiotics have limited efficacy in the presence of heavy bacterial bioburden and biofilm. A novel therapy with activity against bacterial load and biofilm is Reactive Oxygen Species (ROS), oxygen radicals, as an antimicrobial mechanism. ROS can be delivered to the site of infection in various formats. ROS is highly antimicrobial against Gram positive and negative bacteria, viruses and fungi. It prevents and breaks down biofilm. These functions make ROS potentially highly suitable for chronic soft tissue inflammation: wounds, ulcers and burns. In addition to its therapeutic role, ROS could play an important part in surgical prophylaxis, infection prevention and antimicrobial stewardship.